Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Obesity is associated with suppressed growth hormone (GH) concentrations but relatively little is known about insulin-like growth factors(IGFs) and binding proteins for GH and IGFs (GHBP and IGFBPs) and the modulatory effect of GH administration. In a double-blind, crossover design we studied the impact of 5 weeks of placebo or GH administration (0.03 mg.kg-1 body wt.day-1) in nine obese women (mean +/- SEM: age 30.4 +/- 2.4 years; body mass index 37.0 +/- 2.8 kg/m2) on IGF-I, IGF-II, IGFBP-1 and -3 and GHBP. Serum IGF-I (microgram/l) levels were subnormal and increased significantly following GH (117 +/- 16 (placebo) vs 434 +/- 33 (GH) vs 198 +/- 15 (control (p < 0.01)). By contrast, serum IGF-II (microgram/l) levels were in the normal range and remained unchanged (608 +/- 20 (placebo) vs 647 +/- 40 (GH) (NS)). Serum IGFBP-3 was in the normal range and increased significantly during GH treatment, although relatively less than IGF-I, such that the molar ratio between IGF-I and IGFBP-3 increased with GH treatment, whereas the ratio between IGF-I + IGF-II and IGFBP-3 remained unchanged. Serum IGFBP-1 was low in the placebo situation but became further and almost completely suppressed during GH treatment. During a 2-h hyperinsulinemic, euglycemic glucose clamp, IGFBP-1 decreased in the placebo study and remained suppressed during GH. Serum GHBP (nmol/l) levels were elevated substantially compared to non-obese controls (p < 0.001) and did not change during GH treatment (2.37 +/- 0.36 (placebo) vs 2.21 +/- 0.25 (GH) vs 0.80 +/- 0.19 (control)).(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Serum concentrations of insulin-like growth factors (IGFs), IGF binding proteins 1 and 3 and growth hormone binding protein in obese women and the effects of growth hormone administration: a double-blind, placebo-controlled study. 754 82

Sf21 insect cells were infected with recombinant baculovirus containing cDNA for the entire coding region of the mouse growth hormone binding protein (mGHBP). Recombinant (r) mGHBP was expressed at a yield of 17.3 mg/liter/3 days. The molecular size (Mr) of the rmGHBP was approximately 33,000 as estimated by SDS-PAGE. Amino-terminal sequence analysis of the recombinant protein yielded two sequences: one identical to amino acids l- 15 and another corresponding to amino acids 14-21 of the GHR/GHBP. Western blot analysis revealed that this is the same Mr as that of one of the two major Mr forms of serum mGHBP. Deglycosylation of serum mGHBP and recombinant mGHBP caused a shift in the molecular size of both proteins to that expected after removal of all N-linked carbohydrates. Binding characteristics of the recombinant mGHBP to mouse growth hormone were similar to those for serum GHBP. Scatchard analysis showed an equilibrium association constant (Ka) for rmGHBP of 3.8 x 10(8) +/- 0.6 x 10(8) M(-1) (mean +/- SEM, n = 3) and Ka of 9.2 x 10(8) +/- 2.0 x 10(8) M(-1) (mean +/- SEM, n = 3) for the serum mGHBP. In conclusion, this expression system should allow a production of relatively large quantities of mGHBP suitable for physiological studies on the role of this protein.
 ...
PMID:Purification and characterization of recombinant mouse growth hormone binding protein produced in the baculovirus expression system. 917 86

A RIA for mouse GH receptor (mGHR) was developed. A synthetic peptide corresponding to the carboxyl-terminal 14 amino acids of the mGHR (GHR-2 peptide) was used as the antigen for antiserum production. The synthetic peptide was also used as the standard and radioligand in the RIA. The ability of the antiserum to recognize the mGHR was demonstrated by quantitating receptor concentrations in liver and mammary gland from virgin and 15-day-pregnant mice. Serial dilutions of these samples yielded displacement curves parallel to the synthetic peptide. No significant cross-reactivity was seen with serum from virgin or 15-day-pregnant mice, mGH, recombinant mGH-binding protein (mGHBP), a synthetic peptide identical to the hydrophilic tail of mGHBP, or a 14-amino acid synthetic peptide corresponding to amino acids 338-351 of mGHR (GHR-1 peptide). The concentration range of the mGHR RIA was 0.5-200 nM, and the intra- and interassay coefficients of variation were 6.5% and 6.1%, respectively. The concentration of liver GHR increased significantly during pregnancy compared with that in virgin mice, from 0.246 +/- 0.045 pmol/mg protein (mean +/- SEM; n = 5) in the virgin animals to 1.015 +/- 0.159 pmol/mg protein (n = 5) in pregnant mice. In contrast, the mGHR concentration in the mammary gland decreased significantly during pregnancy from 0.606 +/- 0.201 pmol/mg protein (mean +/- SEM; n = 5) to 0.299 +/- 0.027 pmol/mg protein (n = 5). Comparison of the total number of binding sites in livers from virgin and pregnant mice using the GH RRA and the combined results of the mGHR and mGHBP RIAs showed that the two methods gave almost identical results for livers from virgin animals, or 0.363 +/- 0.063 pmol/mg protein (mean +/- SEM; n = 3) and 0.371 +/- 0.008 pmol/mg protein (n = 3) for the GH RRA and the mGHR plus mGHBP RIAs, respectively. However, in livers from pregnant animals, the combined results from the mGHR and mGHBP RIAs were approximately 1.8 times higher than those obtained by the GH RRA, or 6.732 +/- 0.612 pmol/mg protein (mean +/- SEM; n = 3) and 3.693 +/- 0.67 pmol/mg protein (n = 3) for the mGHR plus the mGHBP RIAs and the GH RRA, respectively. The increase in the total GH binding capacity in livers from pregnant mice compared with those from virgin animals was largely due to an increase in the GHBP content. The increase in GHR was only 2.4-fold, or from 0.153 +/- 0.01 pmol/mg protein (mean +/- SEM; n = 3) in virgin mice to 0.364 +/- 0.03 pmol/mg protein (n = 3) in the 15-day-pregnant mice, whereas GHBP increased almost 30-fold during pregnancy, or from 0.218 +/- 0.003 pmol/mg protein (mean +/- SEM; n = 3) in virgin animals to 6.369 +/- 0.607 pmol/mg protein (n = 3) in pregnant mice.
 ...
PMID:Development of a homologous radioimmunoassay for mouse growth hormone receptor. 968 11

Children with simple obesity (SO) show increased linear growth with normal or high serum insulin-like growth factor-I (IGF-I) levels during prepubertal period, despite low GH secretion. We measured IGF-I, IGFBP-1, GHBP and other factors to clarify the hormonal relation between the nutrition and the linear growth in SO and compared these factors with children with normal short stature (NS). Subjects were 23 SO and 19 NS children, and their height standard deviation (SD) scores were 0.7 +/- 0.2 SD and -3.4 +/- 0.3 SD (mean +/- SEM) (P < 0.01), respectively. Oral glucose tolerance test (OGTT) was performed in all the subjects and GH-releasing factor (GRF) test was also performed in 13 of SO and 17 of NS. The peak levels of GH in the GRF test were significantly lower in SO than in NS (12.8 +/- 1.7 vs. 39.8 +/- 6.9 ng/ml) and showed a significantly positive correlation with sigma IGFBP-1 (r = 0.63, P < 0.01). Serum GHBP level and IGF-I level were significantly higher in SO than in NS on pubertal stage matching. There was a positive correlation between GHBP and sigma insulin during OGTT (r = 0.75, P < 0.01). When the sum of the values during OGTT was expressed as sigma, sigma insulin, sigma C-peptide and sigma glucose were significantly higher in SO than in NS on pubertal stage matching. Basal and sigma IGFBP-1 were significantly lower in SO than in NS, but IGFBP-3 levels showed no significant difference between the two groups either in prepuberty or midpuberty. In conclusion, it can be hypothesized that the overnutrition causes hyperinsulinemia which increases GH receptor and IGF-I secretion despite low GH secretion. Hyperinsulinemia also may increase free IGF-I by lowering IGFBP-1. These two mechanism are supposed to be the nutrition related hormonal changes in SO and can explain the growth of SO. In addition, the increased free IGF-I may contribute the decreased GH secretion due to negative feedback in SO.
 ...
PMID:Nutrition related hormonal changes in obese children. 970 Apr 75